Data collection, evaluation and measures

Pharmacovigilance data collection

The BCPH (Belgian Centre for Pharmacovigilance for medicines for Human use) receives both individual reports and compilations of data concerning the adverse effects of medicines. This requires the collaboration of healthcare professionals, marketing authorisation holders and research centres conducting clinical studies with medicines.

- Healthcare professionals (doctors, pharmacists, dentists) can inform the BCPH via the “yellow card” about any suspicion they have concerning adverse effects of medicines they come across in daily practice.

It is nevertheless particularly important to report in the following situations:

Seriousadverse effects: adverse effects that have led to hospitalization or prolongation of the hospitalization, that have been life-threatening, or that have caused death, permanent or significant disability or inability to work, or congenital disorder or malformation.

Unexpectedadverse effects: adverse effects of which the nature, the seriousness and/or the evolution do not correspond with what is mentioned in the Summary of Product Characteristics (SPC).

Suspectedadverse effects: adverse effects that are known but of which the frequency, the seriousness or the result is abnormal.

Switch from one specialty to another during treatment, regardless if it concerns the switch between “original” medicines, from a “generic” to an “original” medicine, from an “original” to a “generic” medicine or between “generic” medicines.

“Inappropriate” or “off-label” use of a medicine.

It is also important to report adverse effects with the so-called “Black triangle drugs”. These include the medicines that contain a new active substance and the new biological medicines. They are indicated by the symbol ▼ in the “Répertoire Commenté des Medicaments”. The ▼ symbol appears for the first 3 years after the marketing of the medicine.

It is important that these ▼ medicines are followed closely as soon as they are marketed. Indeed, at the time that a medicine is authorised, the knowledge about its adverse effects is still limited. The clinical studies conducted for marketing authorisation are mainly intended to show the efficacy of the medicine and have limitations in detecting adverse effects:

the number of patients included in the studies is usually too low to detect rare adverse effects;

the duration of the studies is not long enough to detect adverse effects that appear later on;

the studies usually do not include patients that present a high risk of adverse effects (e.g. pediatric or elderly patients, patients with important comorbidity or polymedication, patients with kidney and liver failure).

The BCPH requests the healthcare professionals to report any suspicions they may have of adverse effects – serious and non serious – with these ▼ medicines, even when there is some doubt about the causality.

Healthcare professionals are encouraged to report all adverse effects they consider as being medically significant, even if they do not meet the above mentioned criteria.

The causality between the suspected medicine and the adverse effect should not necessarily be established to report.

The electronic version of the yellow card for the online reporting of adverse effects is accessible via www.fichejaune.be (in French). Click here for more information (in French).

The paper version of the yellow card can be printed and sent by post to the BCPH. The “paper yellow card” is also available in the “Répertoire Commenté des Médicaments” and three times a year via the Folia Pharmacotherapeutica. In case you wish to receive a paper reporting form, you can request this at any time via the email address: adversedrugreactions@fagg-afmps.be

The paper version can be sent by post to the address mentioned at the back of the yellow card (postage paid by the recipient):

- Patients experiencing an adverse effect after taking a medicine are recommended to contact their doctor, pharmacist or dentist who will fill in the reporting form.

- The marketing authorisation holders (MAH) who are informed about a serious adverse effect, either by healthcare professionals, or by investigators for clinical trials, or by scientific publications, must report this to the BCPH within 15 days of the receipt of the information. In this context a serious adverse effect is defined as an adverse effect that:

At regular intervals, they need to communicate an overview and an evaluation of all reactions, serious and non serious, that occurred both inside and outside the European Union. After 5 years they must provide a global overview in the context of a marketing authorisation renewal dossier.

- Since 2004 promoters of clinical trials are also required to submit all SUSARs (“Suspected Unexpected Serious Adverse Reactions”) that occurred during their clinical trial, both for medicines with and without marketing authorisation. The former are the responsibility of the BCPH. In order to evaluate the safety of the medicines used in clinical trials, the promoter must each year write a safety report about the serious adverse events that happened during a clinical trial and submit it to the BCPH = ASR (Annual Safety Report) - see circular 476 (in French) + Guidelines + Template for the e-submission of PSURs/ARSs + e-submission guidelines .

The BCPH can, if it considers this necessary, ask for a “specific safety report” in which the marketing authorisation holder has to evaluate a specific safety problem concerning a medicine.

Evaluation of the data

The evaluation of the available pharmacovigilance data consists of two parts.

The BCPH evaluates the individual reports of adverse effects (spontaneous reports and SUSARs) but also evaluates the summary reports:

For these tasks, the BCPH is assisted by a team of internal and external experts.

The individual reports are evaluated at regular intervals by a specific working group. The evaluation reports about periodic safety reports and the marketing authorisation renewal dossiers are submitted to a second specific working group.

In case of medicines for which the responsibility for the evaluation is at national level, it is the Commission for Medicines for Human Use that gives the final advice about whether or not the measures suggested by the two working groups can be implemented.

Based on the conclusions of these evaluations on national and European level, the BCPH takes the necessary measures.

Taking measures

If required, after the evaluation of a dossier, the BCPH can take the necessary measures, by:

asking the marketing authorisation holder to modify the information in the « undesirable effects », « special warnings and precautions for use », « contraindications » sections of the SPC (Summary of Product Characteristics) and the leaflet for the patient;

limiting the indications of a medicine and, in some rare cases, suspending or withdrawing the marketing authorisation of a medicine following the decision of the Ministry of Public Health;

in urgent cases informing healthcare professionals about a specific pharmacovigilance problem by means of a press release or a circular.

The authorisation holder can also be requested to send a “Direct Healthcare Professionals Communication” to the concerned healthcare professionals to inform them about the pharmacovigilance problem.

Furthermore, the BCPH collaborates actively with the Belgian Centre for Pharmacotherapeutic Information (in French) which publishes each month a “Communication from the Pharmacovigilance Centre” for healthcare professionals. This describes discussions about adverse effects reported to the BCPH or new data from the specialized literature.